Tandem Pseudopericyclic Reactions: [1,5]-X Sigmatropic Shift/6π-Electrocyclic Ring Closure Converting N-(2-X-Carbonyl)phenyl

Ketenimines into 2-X-Quinolin-4(3H)-ones†

Mateo Alajarı´n,* Marıa-Mar Ortın, Pilar Sa´nchez-Andrada,* and AÄ ngel Vidal

Departamento de Quı´mica Organica, Facultad de Quı´mica, Campus de Espinardo, UniVersidad deMurcia, 30100 Murcia, Spain

alajarin@um.es

ReceiVed June 22, 2006

N-(2-X-Carbonyl)phenyl ketenimines undergo, under mild thermal conditions, [1,5]-migration of the Xgroup from the carbonyl carbon to the electron-deficient central carbon atom of the ketenimine fragment,followed by a 6π-electrocyclic ring closure of the resulting ketene to provide 2-X-substituted quinolin-4(3H)-ones in a sequential one-pot manner. The X groups tested are electron-donor groups, such asalkylthio, arylthio, arylseleno, aryloxy, and amino. When involving alkylthio, arylthio, and arylselenogroups, the complete transformation takes place in refluxing toluene, whereas for aryloxy and aminogroups the starting ketenimines must be heated at 230°C in a sealed tube in the absence of solvent. Themechanism for the conversion of these ketenimines into quinolin-4(3H)-ones has been studied by abinitio and DFT calculations, using as model compoundsN-(2-X-carbonyl)vinyl ketenimines bearingdifferent X groups (X ) F, Cl, OH, SH, NH2, and PH2) converting into 4(3H)-pyridones. Thiscomputational study afforded two general reaction pathways for the first step of the sequence, the [1,5]-X shift, depending on the nature of X. When X is F, Cl, OH, or SH, the migration occurs in a concertedmode, whereas when X is NH2 or PH2, it involves a two-step sequence. The order of migratory aptitudesof the X substituents at the acyl group is predicted to be PH2 > Cl > SH > NH2 > F> OH. The secondstep of the full transformation, the 6π-electrocyclic ring closure, is calculated to be concerted and withlow energy barriers in all the cases. We have included in the calculations an alternative mode of cyclizationof theN-(2-X-carbonyl)vinyl ketenimines, the 6π-electrocyclic ring closure leading to 1,3-oxazines thatinvolves its 1-oxo-5-aza-1,3,5-hexatrienic system. Additionally, the pseudopericyclic topology of thetransition states for some of the [1,5]-X migrations (X) F, Cl, OH, SH), for the 6π-electrocyclizationof the ketene intermediates to the 4(3H)-pyridones, and for the 6π-electrocyclization of the startingketenimines into 1,3-oxazines could be established on the basis of their geometries, natural bond orbitalanalyses, and magnetic properties. The calculations predict that the 4(3H)-pyridones are the thermodynami-cally controlled products and that the 1,3-oxazines should be the kinetically controlled ones.

Introduction

Ketenimines are nitrogenated heterocumulenes [R1-NdCdCR2R3] employed in organic synthesis mainly for the construc-tion of nitrogen-containing heterocycles, via (1) the addition of

nucleophiles1 or radicals2 to its central carbon atom; (2) theattack of electrophiles to its nitrogen atom, which also behavesas a donor atom in the formation of metallicσ complexes;3 and(3) its participation in pericyclic events such as 6π-electrocyclicring closures (ERC), cycloaddition reactions, and sigmatropicrearrangements.1e Among these reactions, sigmatropic rear-rangements in ketenimines have received minor attention, and

† Dedicated to Prof. Marcial Moreno-Man˜as in memoriam.* Corresponding author. Phone:+34 968 367497. Fax:+34 968 364149.

8126 J. Org. Chem.2006, 71, 8126-813910.1021/jo061286e CCC: $33.50 © 2006 American Chemical Society

Published on Web 09/19/2006

they have been scarcely reported. Some examples of [3,3]-,[1,3]- and [1,5]-sigmatropic migrations in ketenimines have beenreported; in most of them the migrating group reaches the centralcarbon atom of the ketenimine.

Concerning the [3,3]-sigmatropic migration, Brannock andBurpitt,4 in a seminal paper in 1965, reported the conversionof N-(2-alkenyl)amides into 4-pentenenitriles by the phosphoruspentachloride/triethylamine combination of reagents. TheypostulatedN-(2-alkenyl) ketenimines as reaction intermediates,suggesting that these species undergo a 3-aza-Claisen rear-rangement to the unsaturated nitriles. Afterward, Walters5 andsome of us6 carried out an extensive investigation of this [3,3]-rearrangement in a variety of new 2-(alkenyl) ketenimines,which included the development of new methods for thesynthesis of this type of ketenimines, an experimental study ofthe stereocontrol of this reaction, and a computational study ofthe 3-aza-Claisen rearrangement of 3-aza-1,2,5-hexatrienes. Thisthermally induced 3-aza-Claisen rearrangement ofN-(2-alkenyl)ketenimines has been used as a key step in efficient asymmetricsyntheses of the chiral natural products (+)-canadensolide, (+)-santolinolide B, and (-)-santolinolide A.7

The more important research works dealing with [1,3]-sigmatropic shifts in ketenimines have been reported byWentrup,8a-h who carried out an extensive study of the reversibleC-acyl ketenimine to imidoyl ketene rearrangement, via [1,3]-sigmatropic shifts of a variety of atoms or groups of atoms underflash vacuum pyrolysis (FVP) conditions. In these processes,

when (N-aryl)imidoyl ketenes are formed they underwent further6π-electrocyclization to quinolin-4(1H)-ones (Scheme 1).8b,d-f,9

To our knowledge, only three examples of [1,5]-sigmatropicshifts in ketenimines have been described so far, and all of theminvolve a [1,5]-hydrogen atom transfer to the central carbon ofthe ketenimine. Goerdeler10 reported thatC-imidoyl keteniminesunderwent, at room temperature, a [1,5]-H shift followed byERC to yield dihydropyrimidines. On the other hand, Foucaud11

demonstrated that in refluxing dichloromethaneN-imidoylketenimines converted into pyrrolotriazines by a consecutive[1,5]-H shift/intramolecular [4+ 2]-cycloaddition. More re-cently, Wentrup12 published thatN-aryl ketenimines bearingmethyl groups at the ortho position suffer, under flash vacuumthermolysis conditions, a facile [1,5]-H shift and subsequentelectrocyclization to dihydroquinolines.

In the frame of a systematic development of new reactionsof ketenimines, we targeted the synthesis of a variety ofN-(2-X-carbonyl)phenyl ketenimines (Chart 1), with the aim ofexamining the viability of the [1,5]-migration of diverse Xgroups from the carbonyl carbon to the electron-deficient centralcarbon atom of the ketenimine fragment. We focused on testingthe sigmatropic migration of electron-donor groups, such asalkylthio, arylthio, arylseleno, aryloxy, amino, and halides, giventhe electrophilic character of the presumed migration terminus.

In this paper, we report that in fact such ketenimines undergoa facile [1,5]-sigmatropic migration of the X group under mildthermal conditions and a subsequent 6π-electrocyclic ringclosure of the resulting ketene to afford 2-X-substituted quinolin-4(3H)-ones. Furthermore, we have carried out a computationalstudy in order to gain insight on the mechanism of thesetransformations and to evaluate the relative migratory aptitudeof the different X groups. In a previous communication, wehave reported thatN-[2-(alkyl- or arylthio)carbonyl]phenylketenimines undergo cyclization to afford 2-alkyl(aryl)thio-

(1) For reviews on the chemistry of ketenimines, see: (a) Krow, D. R.Angew. Chem., Int. Ed. Engl.1971, 10, 435-449. (b) Gambaryan, N. P.Usp. Khim.1976, 45, 1251-1268. (c) Dondoni, A.Heterocycles1980, 14,1547-1566. (d) Barker, M. W.; McHenry, W. E. InThe Chemistry ofKetenes, Allenes and Related Compounds; Patai, S., Ed.; Wiley-Inter-science: Chichester, U.K., 1980; Part 2, p 701. (e) Alajarı´n, M.; Vidal, A.;Tovar, F.Targets Heterocycl. Syst.2000, 4, 293-326.

(2) (a) Alajarın, M.; Vidal, A.; Ortın, M.-M. Tetrahedron Lett.2003,44, 3027-3030. (b) Alajarı´n, M.; Vidal, A.; Ortın, M.-M. Org. Biomol.Chem. 2003, 1, 4282-4292. (c) Alajarı´n, M.; Vidal, A.; Ortın, M.-M.;Bautista, D.New J. Chem.2004, 28, 570-577. (d) Alajarı´n, M.; Vidal, A.;Ortın, M.-M.; Bautista, D.Synlett2004, 991-994.

(3) (a) Aumann, R.Chem. Ber.1993, 126, 1867-1872. (b) Merlic, C.A.; Burns, E. E.Tetrahedron Lett.1993, 34, 5401-5404.

(4) Brannock, K. C.; Burpitt, R. D.J. Org. Chem.1965, 30, 2564-2565.

(5) (a) Walters, M. A.; McDonough, C. S.; Brown, P. S., Jr.; Hoem, A.B. Tetrahedron Lett.1991, 32, 179-182. (b) Walters, M. A.; Hoem, A.B.; Arcand, H. R.; Hegeman, A. D.; McDonough, C. S.Tetrahedron Lett.1993, 34, 1453-1456. (c) Walters, M. A.; Hoem, A. B.J. Org. Chem.1994, 59, 2645-2647. (d) Walters, M. A.J. Am. Chem. Soc.1994, 116,11618-11619. (e) Walters, M. A.J. Org. Chem.1996, 61, 978-983.

(6) (a) Molina, P.; Alajarı´n, M.; Lopez-Leonardo, C.Tetrahedron Lett.1991, 32, 4041-4044. (b) Molina, P.; Alajarı´n, M.; Lopez-Leonardo, C.;Alcantara, J.Tetrahedron1993, 49, 5153-5168.

(7) Nubbemeyer, U.Synthesis1993, 1120-1128.(8) (a) Cheikh, A. B.; Chuche, J.; Manisse, N.; Pommelet, J. C.; Netsch,

K.-P.; Lorencak, P.; Wentrup, C.J. Org. Chem.1991, 56, 970-975. (b)Kappe, C. O.; Kollenz, G.; Leung-Toung, R.; Wentrup, C.J. Chem. Soc.,Chem. Commun.1992, 487-488. (c) Kappe, C. O.; Kollenz, G.; Netsch,K.-P.; Leung-Toung, R.; Wentrup, C.J. Chem. Soc., Chem. Commun.1992,488-490. (d) Fulloon, B.; El-Nabi, H. A. A.; Kollenz, G.; Wentrup, C.Tetrahedron Lett.1995, 36, 6547-6550. (e) Fulloon, B. E.; Wentrup, C.J.Org. Chem.1996, 61, 1363-1368. (f) Ramana Rao, V. V.; Wentrup, C.J.Chem. Soc., Perkin Trans. 11998, 2583-2586. (g) Wentrup, C.; RamanaRao, V. V.; Frank, W.; Fulloon, B. E.; Moloney, D. W. J.; Mosandl, T.J.Org. Chem.1999, 64, 3608-3619. (h) Finnerty, J. J.; Wentrup, C.J. Org.Chem.2004, 69, 1909-1918. For other papers dealing with [1,3]-migrationin ketenimines, see: (i) Aumann, R.; Heinen, H.Chem. Ber.1988, 121,1739-1743. (j) Clarke, D.; Mares, R. W.; McNab, H.J. Chem. Soc., Chem.Commun1993, 1026-1027. (k) Clarke, D.; Mares, R. W.; McNab, H.J.Chem. Soc., Perkin Trans. 11997, 1799-1804. (l) Amsallem, D.; Mazie`res,S.; Piquet-Faure´, V.; Gornitzka, H.; Baceiredo, A.; Bertrand, G.Chem.-Eur. J. 2002, 8, 5306-5311.

(9) The Conrad-Limpach synthesis of quinolones by pyrolysis of estersprobably proceeds via imidoyl ketene intermediates: Conrad, M.; Limpach,L. Ber. Dtsch. Chem. Ges.1887, 20, 944-948. The first report on theobservation of imidoyl ketenes in quinolone synthesis: Briehl, H.; Adelheid,L.; Wentrup, C.J. Org. Chem.1984, 49, 2772-2779.

(10) Goerdeler, J.; Lindner, C.; Zander, F.Chem. Ber.1981, 114, 536-548.

(11) Morel, G.; Marchand, E.; Foucaud, A.J. Org. Chem.1985, 50, 771-778.

(12) Ramana Rao, V. V.; Fulloon, B. E.; Bernhardt, P. V.; Koch, R.;Wentrup, C.J. Org. Chem.1998, 63, 5779-5786.

SCHEME 1. [1,3]-Sigmatropic Shifts in C-Acyl Ketenimines

CHART 1. N-(2-X-Carbonyl)phenyl Ketenimines

Tandem Pseudopericyclic Reactions in Ketenimines

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quinolin-4(3H)-ones by means of a consecutive 1,5-migrationof the alkyl(aryl)thio group/6π-electrocyclization.13

Results and Discussion

Experimental Study. First, we tested the migration of alkyl-(aryl)thio groups inN-[2-alkyl(aryl)thiocarbonyl]phenyl keten-imines4a-l.14 The reaction of 2-azidobenzoyl chloride1a and2-azido-5-chlorobenzoyl chloride1b with alkylthiols and aryl-thiols, in dichloromethane solution, in the presence of a slightexcess of DMAP, afforded theS-alkyl and S-aryl 2-azidot-hiobenzoates2a-j . The treatment of the 2-azidothiobenzoates2a-j , in diethyl ether solution, with triphenylphosphine providedthe 2-(triphenylphosphoranylideneamino)thiobenzoates3a-j .The reaction of triphenylphosphazene3a (R1 ) H; X )4-CH3C6H4S), in dichloromethane solution at room temperature,with a stoichiometric amount of diphenylketene gave ketenimine4a (R1 ) H; X ) 4-CH3C6H4S; R2 ) Ph), which was purifiedby column chromatography on silica gel, isolated, and fullyidentified.14 When a toluene solution of4awas heated at refluxtemperature for approximately 1 h, an IR spectra of the reactionmixture showed the total disappearance of the cumulenic bandaround 2000 cm-1 associated with the NdCdC grouping, andfrom the resulting crude material 2-(4-methylphenylthio)-3,3-diphenylquinolin-4(3H)-one 5a (R1 ) H; X ) 4-CH3C6H4S;R2 ) Ph) was isolated by column chromatography as the onlyreaction product (Scheme 2).

Following this initial experiment, the aza-Wittig reactions ofa series of organosulfur iminophosphoranes3a-j with diphe-nylketene and methylphenylketene were carried out in toluenesolution, at room temperature, to give the correspondingketenimines4a-l, whose formation was confirmed by IR spectraof the reaction mixtures. The heating of toluene solutionscontaining ketenimines4a-l at reflux temperature for 1 h

provided the respective 2-alkyl(aryl)thioquinolin-4(3H)-ones5a-l in acceptable yields (Scheme 2, Table 1). The conversions4a-l f 5a-l also took place at room temperature, althoughmost of these reactions required up to 48 h to be completed.The structural determination of the 2-alkyl(aryl)thioquinolin-4(3H)-ones5a-l was achieved following their analytical andspectral data and was unequivocally established by the X-raystructure determination of a monocrystal of5a (R1 ) H; X )4-CH3C6H4S; R2 ) Ph).14

Next, we preparedN-(2-arylselenocarbonyl)phenyl keten-imines4m-o from theSe-aryl 2-azidoselenobenzoates2k,l viaa simple chemical sequence. Thus, treatment of solutions ofdiphenyl diselenide and bis(4-methoxyphenyl) diselenide, inanhydrous ethanol, with sodium borohydride provided sodiumbenzeneselenolate and 4-methoxybenzeneselenolate, which re-acted with 2-azidobenzoyl chloride1a, leading to the respective

(13) Alajarın, M.; Ortın, M.-M.; Sanchez-Andrada, P.; Vidal, A.; Bautista,D. Org. Lett. 2005, 7, 5281-5284.

(14) The experimental work related with the [1,5]-migration of alkyl-(aryl)thio groups inN-[2-alkyl(aryl)thiocarbonyl]phenyl ketenimines hasbeen reported in our preliminary communication, ref 13.

SCHEME 2. Synthesis of Quinolin-4(3H)-ones 5a

a Reagents and conditions: (a) For X) SR3: R3SH, DMAP, CH2Cl2, rt, 5 h. For X) SeAr: ArSeSeAr, NaBH4, EtOH, rt, 3 h. For X) OAr: ArOH,DMAP, CH2Cl2, rt, 5 h. For X) NR3R4: R3R4NH, pyridine, 0°C, 1.5 h. (b) For X) SR3, OAr, NR3R4: PPh3, Et2O, rt, 16 h. For X) SeAr: PPh3, toluene,rt, 4 h. (c) For X) SR3, SeAr: PhR2CdCdO, toluene, rt, 15 min. For X) OAr, NR3R4: PhR2CdCdO, CH2Cl2, rt, 15 min. (d) For X) SR3, SeAr:toluene, reflux, 1 h. For X) OAr, NR3R4: neat, sealed tube, 230°C, 1 h.

TABLE 1. Quinolin-4(3H)-ones 5

compd R1 X R2 yield (%)

5a H 4-CH3C6H4S Ph 745b H 4-CH3C6H4S Me 525c H 4-CH3OC6H4S Ph 895d H 4-(C5H5N)S Ph 795e Cl 4-CH3C6H4S Ph 975f Cl 4-CH3OC6H4S Ph 955g Cl 4-CH3OC6H4S Me 765h H 4-CH3OC6H4CH2S Ph 835i H C6H5(CH3)CHS Me 58a

5j Cl 4-CH3OC6H4CH2S Ph 515k H C6H5CH2CH2S Ph 855l H 2-IC6H4CH2CH2S Ph 905m H C6H5Se Ph 625n H C6H5Se Me 605o H 4-CH3OC6H4Se Ph 365p H 4-CH3C6H4O Ph 425q H 4-CH3C6H4O Me 285r H 3,4-(CH3O)2C6H3O Ph 365s H 3,4-(CH3O)2C6H3O Me 255t H (CH3)2N Ph 365u H C6H5(CH3)N Ph 305v H (4-CH3C6H4)2N Ph 25

a Isolated as a 1:1 mixture of two diastereoisomers.

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8128 J. Org. Chem., Vol. 71, No. 21, 2006

formation ofSe-phenyl 2-azidoselenobenzoate2k (R1 ) H; X) C6H5Se) andSe-(4-methoxyphenyl) 2-azidoselenobenzoate2l (R1 ) H; X ) 4-CH3OC6H4Se), in very low yields, whereasthe major product isolated from these reactions was ethyl2-azidobenzoate.15 The sequential treatment at room tempera-ture, and in the same reaction flask, of toluene solutions of the2-azidoselenobenzoates2k,l with triphenylphosphine and diphe-nylketene or methylphenylketene led to the correspondingketenimines4m-o, which converted into the respective 2-ar-ylselenoquinolin-4(3H)-ones5m-o when their toluene solutionswere heated at reflux temperature for 1 h (Scheme 2, Table 1).

The reaction of 2-azidobenzoyl chloride1a with 4-meth-ylphenol and 3,4-dimethoxyphenol, in dichloromethane solutionin the presence of DMAP, and the subsequent Staudingerreaction of the aryl 2-azidobenzoates2m,n with triphenylphos-phine, in diethyl ether, provided in a straightforward mannerthe aryl 2-(triphenylphosphoranylideneamino)benzoates3m,n.Our first try at the [1,5]-migration of aryloxy groups inN-(2-aryloxycarbonyl)phenyl ketenimines was carried out by heatingin either refluxing toluene oro-xylene solutions of theC,C-diphenyl ketenimine4p (R1 ) H; X ) 4-CH3C6H4O; R2 ) Ph),generated by reaction of compound3m (R1 ) H; X )4-CH3C6H4O) with diphenylketene in these solvents. We couldestablish that after 48 h under both reaction conditions com-pound4p remained unaltered, and the same result was obtainedwhen 4p was heated for the same time at 180°C in toluenesolution in a sealed tube. Afterward, ketenimine4p wasgenerated in dichloromethane and, after removing the solvent,the mixture containing this ketenimine and the triphenylphos-phine oxide was heated at 230°C in a sealed tube up to thetotal disappearance of the cumulenic band in its IR spectrum,approximately 1 h. The material obtained from this thermaltreatment was chromatographed, thus resulting in the isolationof pure 2-(4-methylphenyloxy)-3,3-diphenylquinolin-4(3H)-one5p, in 42% yield. The application of this procedure to theN-(2-aryloxycarbonyl)phenyl ketenimines4q-s yielded the corre-sponding 2-aryloxyquinolin-4(3H)-ones 5q-s in low yields(Scheme 2, Table 1).

Finally, we were also able to achieve the [1,5]-shift of aminogroups inN-(2-carbamoyl)phenyl ketenimines. The acylationof dialkyl, alkylaryl, or diaryl substituted secondary amines with2-azidobenzoyl chloride1a led to the 2-azidobenzamides2o-q, which by the habitual methodology were converted into theirrespectiveN-(2-carbamoyl)phenyl ketenimines4t-v. We couldconvert ketenimines4t-v into the 2-aminoquinolin-4(3H)-ones5t-v only when these heterocumulenes were heated at 230°Cin a sealed tube in the absence of solvent, although the yieldsof these transformations were also low (Scheme 2, Table 1).

At this point of the discussion, it is worth mentioning thatalthough we planned to test the migration of bromine and

chlorine atoms in theN-(2-bromocarbonyl)phenyl ketenimine4w and theN-(2-chlorocarbonyl)phenyl ketenimine4x, respec-tively (Chart 2), unfortunately the strategies that we attemptedfor the preparation of these two ketenimines failed. Thesesynthetic approaches involved either the use of starting materialsbearing an acyl halide function or the generation of this functionin the last step, in the presence of the ketenimine grouping.

We assume that the mechanism of the transformation of theketenimines4 into the quinolin-4(3H)-ones5 is initiated by the[1,5]-migration of the X group from the carbonyl carbon to thecentral carbon atom of the ketenimine moiety to give the imidoylketenes6, which are further converted into the reaction products5 through a 6π-electrocyclic ring closure of their conjugated3-azahexatriene fragment (Scheme 3). It is also conceivable thatthe N-(2-X-carbonyl)phenyl ketenimines4 may experiencecyclization to the 3,1-benzoxazines7 via a 6π-electrocyclizationinvolving their conjugated 1-oxa-5-azahexatrienic system. How-ever, it does not seem to be the case, as compounds7 werenever detected in the1H NMR spectra of the crude materialsobtained from the thermal treatment of ketenimines4. Giventhat all the reactions in Scheme 3 can be chemical equilibria,the exclusive formation of quinolin-4(3H)-ones5 in the thermaltreatment of ketenimines4 may be a consequence of prevailingthermodynamic versus kinetic control. At first sight, compounds5 seem more stable, on thermodynamic grounds, than theo-quinonoid benzoxazines7. This matter will be treated in depthin the following sections.

Computational Study. For simplicity, to model the trans-formation of the ketenimines4 into the quinolin-4(3H)-ones5presented in the experimental part of this work, we selectedthe more simple structures8c-e, where the vinyl group joiningthe acyl and ketenimine functions models the benzene ring ofthe ketenimines4 and the OH, SH, and NH2 groups model theOAr, SR3, and NR3R4 groups. In our previous communication,13

we have shown computationally that the transformation ofketenimine8d (X ) SH) into 2-thiohydroxy-4(3H)-pyridone9d occurs by a two-step pathway that starts with the [1,5]-shiftin the SH group leading to an intermediate imidoyl ketene10d,which in a second step undergoes an electrocyclic ring closure

(15) We did not succeed in the synthesis of theSe-aryl 2-azidosele-nobenzoates2k,l by using other well-established reaction conditions forthe preparation of selenoesters, such as those used in the followingarticles: (a) Grieco, P. A.; Jaw, J. Y.J. Org. Chem.1981, 46, 1215-1217.(b) Nicolaou, K. C.; Petasis, N. A.; Claremon, D. A.Tetrahedron1985,41, 4835-4841. (c) Gais, H.-J.Angew. Chem., Int. Ed. Engl.1977, 16,244-246. (d) Ireland, R. E.; Norbeck, D. W.; Mandel, G. S.; Mandel, N.S. J. Am. Chem. Soc.1985, 107, 3285-3294. Probably theo-azido groupof 1 interferes with the expected substitution at the acyl group. Only amodification of the experimental procedure described by Odom for thepreparation of selenoesters from acyl chlorides and benzeneselenolates,generated by reaction of diaryl diselenides and sodium borohydride, providedthe Se-aryl 2-azidoselenobenzoates2k,l, although in very low yields, see:(e) Mullen, G. P.; Luthra, N. P.; Dunlap, R. B.; Odom, J. D.J. Org. Chem.1985, 50, 811-816.

CHART 2. N-(2-Bromocarbonyl)phenyl Ketenimine 4w andN-(2-Chlorocarbonyl)phenyl Ketenimine 4x

SCHEME 3. Proposed Mechanism for the Conversion 4f5

Tandem Pseudopericyclic Reactions in Ketenimines

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to provide the 4(3H)-pyridone9d. In this mechanistic schemethe rate-determining step was the [1,5]-sigmatropic rearrange-ment of the SH group. To gain insight on the migrating aptitudesof the different X groups and a deeper understanding of themechanistic aspects of this process, we have considered in thisstudy, besides the migrating groups above-mentioned, thefluorine and chlorine atoms and the PH2 group, by includingthem on the ketenimines8a, 8b, and8f, respectively.

We have explored the potential energy surface associated withthe transformation of the ketenimines8a-f into the 4(3H)-pyridones9a-f (Scheme 4, path A). On the other hand, the1-oxo-5-aza-1,3,5-hexatrienic system present in ketenimimes8enables these compounds to experience a 6π-electrocyclic ringclosure, leading to the 2-methylene-6-substituted-1,3-oxazines11 (path B). Due to its presumable pseudopericyclic nature, thisprocess is expected to occur easily,16 and consequently it couldcompete with path A. This is the reason we have also includedin our calculations this alternative mode of cyclization of theketenimines8.

It is worth emphasizing from the beginning of this discussionthat the structural characteristics of the ketenimines8a-f andthe ketene intermediates10a-f open the possibility that the[1,5]-sigmatropic rearrangements and the two 6π-electrocyclicring closures delineated in Scheme 4 (8a-ff11a-f and10a-ff9a-f) can take place in a pseudopericyclic way. Note thatin the three reactions in that scheme a more or less nucleophilicatom becomes linked to the central carbon of a heterocumulenefunction. Thus, with the aim of knowing the precise nature ofthese transformations, in this computational study we have paidspecial attention to the characterization of the orbital topologyof their respective transition states.

Figures 1 and 4 display the qualitative reaction profiles atthe B3LYP/6-31+G* theoretical level and the location of thestationary points for the transformation of ketenimines8a-finto 9a-f and 11a-f. Figures 2, 3, and 5-7 show thegeometries of the transition statesTS1a-d, TS2a-d, andTS3a-f and the stationary points found in the transformations8e,ff9e,f/11e,f, including relevant bond distances. Table 2includes the relative energies of the stationary points at theB3LYP/6-31+G*//B3LYP/6-31+G* theoretical level and theenergy barriers. Zero-point vibrational energy corrections have

been applied, but not scaled. We will comment only on theresults obtained at the B3LYP/6-31+G* theoretical level, unlessotherwise stated.

Path A. Transformation of Ketenimines 8a-f into the4(3H)-Pyridones 9a-f. Surprisingly, depending on the natureof the migrating group X, we have found two different generalpathways for the conversion of ketenimines8a-f into the 4(3H)-pyridones9a-f. Thus, when X is F, Cl, OH, or SH (8a-d),the [1,5]-X shift occurs in a concerted mode, whereas when Xis NH2 or PH2 (8eand8f) the migration of the NH2 or the PH2

group involves a two-step mechanistic scheme. We next discussseparately these two reaction pathways, concerted and stepwise.

Concerted [1,5]-X Sigmatropic Rearrangement of Keten-imines 8a-d to Ketenes 10a-d and Subsequent 6π-Elec-trocyclic Ring Closure Leading to 4(3H)-Pyridones 9a-d.The intensive search along both HF/6-31G* and B3LYP/6-31+G* potential energy surfaces revealed a similar mechanismfor the transformation of the four ketenimines8a-d (X ) F,Cl, OH, and SH) into their respective 4(3H)-pyridones9a-d.The first step consists of a [1,5]-shift of the X group, via thetransition structuresTS1a-d (Figure 2), leading to the inter-mediate ketenes10a-d, which in a second step undergo anelectrocyclic ring closure, through the transition statesTS2a-d, to give the final 4(3H)-pyridones9a-d.

The computed energy barriers for the first step, the [1,5]-Xshift, range from 22.90 (X) OH) to 15.76 (X) Cl) kcal‚mol-1,the process being slightly endothermic (by 3.56-10.23kcal‚mol-1). The energy barrier for the prototypical [1,5]-H shiftin cis-1,3-pentadiene, which has been calculated to be 32.6kcal‚mol-1 from thes-cis conformer,17 is significantly higherthan those corresponding to the present [1,5]-X shifts convertingthe ketenimines8a-d into the ketenes10a-d. The geometriesof the transition statesTS1a-d are planar or nearly planar. Incontrast, the transition structure of the suprafacial [1,5]-H shiftin 1,3-pentadiene (TS1ref, see Supporting Information) re-sembles a slightly flattened cyclohexane ring,18 the migratinghydrogen projecting out of the plane and the HCCC dihedralangle being 27.6°. The molecular skeletons ofTS1aandTS1bare essentially planar, the F and Cl atoms migrating in themolecular plane (see the values of the dihedral angles in Figure2), where the LUMO of the ketenimine moiety is placed. Thesituation is similar inTS1c(X ) OH), but in this case, the OHgroup projects slightly out the plane. InTS1d (X ) SH) themolecular skeleton deviates more notably from planarity andthe values of the SC1N3C4 and SC6C5C4 dihedral angles are28.9° and 18.0° respectively.

The computed energy barriers for the second step in thecyclization 8a-df9a-d, that is, the 6π-electrocyclic ringclosure of10a-d to 9a-d, are very low, ranging from 1.51 to5.20 kcal‚mol-1, and in all the cases the process is exothermic.By comparing the values of the barriers associated with thesering closures with that calculated for the archetypical 6π-electrocyclic ring closure of 1,3,5-hexatriene to 1,3-cyclohexa-diene, which has been computed to be 26.6 kcal mol-1,19 it isclear that the barriers for the cyclization of ketenes10a-d to

(16) We have reported that a similar ring closure transformingN-â-(methyleneaminoacyl)vinyl ketenimine into 6-methyleneamino-2-methylene-1,3-oxazine takes place trough a transition state of pseudopericyclic topologyand low energy barrier; see: Alajarı´n, M.; Sanchez-Andrada, P.; Vidal,A.; Tovar, F.J. Org. Chem.2005, 70, 1340-1349.

(17) (a) Saettel, N. J.; Wiest, O.J. Org. Chem.2000, 65, 2331-2336.(b) Hess, B. A.; Baldwin, J. E.J. Org. Chem.2002, 67, 6025-6033. (c)Jursic, B. S.THEOCHEM1998, 423, 189-194. (d) Jensen, F.; Houk, K.N. J. Am. Chem. Soc.1987, 109, 3139-3140.

(18) For comparative purposes, we have also optimized the transitionstate corresponding to the [1,5]-H migration in 1,3-pentadiene, although ithas been extensively studied previously by others (see ref 17 and referencescited herein).

SCHEME 4. Intramolecular Cyclization Modes for theKetenimines 8a-f

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the 4(3H)-pyridones9a-d are unusually small. The geometriesof TS2a-d show their monorotatory nature (the hydrogen atC5, C4, C5, C6, and O12 are in the same plane; see Figure 3).The analysis of the imaginary frequency associated with eachtransition structure revealed that the nuclear movements do notinvolve rotation around the C5-C6 π system but only aroundthe C1-C2 ones. Both, the geometry of the transition states

TS2a-d and the small values of the energy barriers indicatethat their orbital topology could be qualified as pseudopericyclic(see below).

Two-Step [1,5]-X Sigmatropic Rearrangement of Keten-imines 8e,f to Ketenes 10e,f and Subsequent 6π-ElectrocyclicRing Closure Leading to 4(3H)-Pyridones 9e,f.The intensivesearch along the HF/6-31G* potential energy surface associated

FIGURE 1. Qualitative reaction profiles at the B3LYP/6-31+G* level for the transformation of the ketenimines8a-d into the 4(3H)-pyridones9a-d and the 1,3-oxazines11a-d.

FIGURE 2. B3LYP/6-31+G*-optimized geometries of the transitionstructures found in the transformation of the ketenimines8a-d intothe ketenes10a-d.

FIGURE 3. B3LYP/6-31+G*-optimized geometries of the transitionstructures found in the cyclization of the ketenes10a-d to the 4(3H)-pyridones9a-d.

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with the transformation of ketenimines8eand8f into the 4(3H)-pyridones9eand9f revealed that the [1,5]-migration of the NH2

and PH2 groups leading to the ketene intermediates does notoccur in a concerted mode, but instead taking place in twosteps.20 The first one consists of the nucleophilic attack of thelone pair at the nitrogen or phosphorus atom onto the centralcarbon atom of the ketenimine moiety, through the transitionstructuresTS1Ae,f, to provide the dipolar intermediatesINTe,f.In a second step the breaking of the C6-X bond takes place,via the transition statesTS1Be,f, leading to the ketenes10e,f(see Scheme 5). The ability of nitrogen and phosphorus to existin a tetracoordinated state could explain why in these cases the[1,5]-shift takes place involving the formation of the zwitterionicintermediates. The ring closure of ketenes10e,f occurs via thetransition statesTS2e,f, whose geometries are analogous to thosefound in TS2a-d. The exploration of the potential energysurface at the correlated B3LYP/6-31+G* level led to the sameresults, except forTS1Be, the ketene intermediate10e, and thetransition structureTS2e, which could not be optimized at thattheoretical level. Instead, we found only a transition structure

TS4einvolving the simultaneous breaking of the C6-N7 bondand the formation of the C2-C6 bond. The IRC calculationsshowed thatTS4econnects with the dipolar intermediateINTeand the 2-amino-4(3H)-pyridone9e (see Scheme 6 and path Ain Figure 4).

At the B3LYP/6-31+G* theoretical level the computedenergy barriers for the formation of the polar intermediatesINTe,f from the ketenimines8e,f were 18.09 and 14.38kcal‚mol-1 respectively, both processes being slightly endo-thermic. The energy barrier for the breaking of the C6-P7 bondin INTf , leading to the ketene10f, is very low (3.52 kcal‚mol-1).The conversionINTef10e, at the HF/6-31G* theoretical level,involves an almost imperceptible barrier (0.64 kcal‚mol-1). Atthe B3LYP/6-31+G* level, the energy barrier calculated forthe transformation of the polar intermediateINTe into 2-amino-4(3H)-pyridone (9e), via the transition structureTS4e, was only3.45 kcal‚mol-1. The overall processes transforming the keten-imines8e,f into the final 4(3H)-pyridones9e,f are exothermicby 27.58 and 27.44 kcal‚mol-1, respectively. The stationarypoints of these transformations are represented in Figures 5 and6.

At this point, we can establish, according to the energybarriers computed for the [1,5]-shifts studied in this work (see∆E1 and∆E1

A in Table 2), the order of migratory aptitudes ofthe X substituents at the acyl group in ketenimines8a-f, whichis predicted to be, from highest to lowest, the following: PH2

> Cl > SH > NH2 > F> OH.The groups based on the second-row elements (PH2, Cl, SH)

show higher migratory aptitude than those based on first-rowelements (NH2, F, OH), a fact that can be rationalized by takinginto account the values of the C-X bond dissociation energies,which are smaller for C-P, C-Cl, and C-S than for C-N,C-F, and C-O, respectively. On the other hand, as these [1,5]-

(19) (a) Rodrı´guez-Otero, J. J. Org. Chem. 1999, 64, 6842-6848. (b)Jiao, H.; Schleyer, P. v. R.J. Am. Chem. Soc. 1995, 117, 11529-11535.(c) Evanseck, J. D.; Thomas, B. E., IV; Spellmeyer, D. C.; Houk, K. N.J.Org. Chem.1995, 60, 7134-7141. (d) Jefford, C. W.; Bernardinelli, G.;Wang, Y.; Spellmeyer, D. C.; Buda, A.; Houk, K. N.J. Am. Chem. Soc.1992, 114, 1157-1165. (e) Baldwin, J. E.; Reddy, V. P.; Schaad, L. J.;Hess, B. A.J. Am. Chem. Soc. 1988, 110, 8554-8555.

(20) (a) An analogous finding was accomplished in the study of the effectof several substituents in the vinylketene-acylallene rearrangement reportedby Wentrup et al.: the [1,3]-shift in the dimethylamino group takes placeinvolving the formation of a zwitterionic intermediate. See: Bibas, H.;Wong, M. W.; Wentrup, C.Chem.-Eur. J.1997, 3, 237-248. (b) Recently,Wentrup et al. have also found zwitterionic intermediates in the [1,3]-shiftsof amino and dimethylamino groups in the imidoylketene-acyl keteniminerearrangement; see: Finnerty, J. F.; Wentrup, C.J. Org. Chem. 2005, 70,9735-9739.

FIGURE 4. Qualitative reaction profiles at the B3LYP/6-31+G* level for the transformation of the ketenimines8e,f into the 4(3H)-pyridones9e,fand the 1,3-oxazines11e,f.

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shifts involve the interaction between a high-lying orbital ofthe migrating group and the low-lying LUMO of the ketenimine(see below), the activation barriers depending on the respectivenucleophilicities and electrophilicities of the reacting centers.Therefore, as the second-row elements are known to be morenucleophilic than those of the first-row, this fact serves toexplain why the energy barriers for the migration of the second-row atoms are lower than those of their first-row isovalentcounterparts.

It is worthy to remark here that Wentrup and others havesystematically studied a number of equilibria between acylketenimines and imidoyl ketenes by sigmatropic [1,3]-rear-rangements of H and other atoms or groups and established theirpseudopericyclic nature and the relative migratory aptitude ofdifferent groups.20a,21 However, [1,5]-sigmatropic rearrange-ments in heterocumulenes as such here reported have not beendisclose up to now.

Path B: Cyclization of Ketenimines 8a-f to the 1,3-Oxazines 11a-f. Our calculations show that the alternativemode of cyclization of the ketenimines8a-f, its 6π-electrocyclicring closure leading to 2-methylene-6-substituted-1,3-oxazines11a-f, takes place via the transition structuresTS3a-f (Figure7). Interestingly, the geometry of all these transition structuresis planar, and the analysis of their imaginary frequencies showedthe nonrotatory nature of these cyclizations. The computedenergy barriers (∆E3) are very low (from 6.35 to 9.62kcal‚mol-1), and their exothermicities range from 0.22 to 11.85kcal‚mol-1.

From the reaction profiles in Figures 1 and 4 and the valuesof the energy barriers gathered in Table 2, the followingconclusions can be drawn: (i) the 4(3H)-pyridones9a-f arepredicted to be the thermodynamically controlled products,

(21) (a) Koch, R.; Wentrup, C.Org. Biol. Chem. 2004, 2, 195-199. (b)Nguyen, M. T.; Landuyt, L.; Nguyen, H. M. T.Eur. J. Org. Chem.1999,401-407. For similar [1,3]-sigmatropic shifts occurring in other heterocu-mulenes see: (c) Koch, R.; Wentrup, C.J. Chem. Soc., Perkin Trans. 22000, 1846-1850. (d) Ammann, J. R.; Flammang, R.; Wong, M. W.;Wentrup, C.J. Org. Chem. 2000, 65, 2706. (e) Wong, M. W.; Wentrup, C.J. Org. Chem. 1994, 59, 5279-5285. (f) Bibas, H.; Wong, M. W.; Wentrup,C. J. Am. Chem. Soc. 1995, 117, 9582-9583. (g) Finnerty, J.; Andraos, J.;Yamamoto, Y.; Wong, M. W.; Wentrup, C.J. Am. Chem. Soc. 1998, 120,1701-1704.

FIGURE 5. B3LYP/6-31+G*-optimized geometries of the stationarypoints found in the cyclization of the ketenimine8e to the 4(3H)-pyridone9e.

FIGURE 6. B3LYP/6-31+G*-optimized geometries of the stationarypoints found in the cyclization of the ketenimine8f to the 4(3H)-pyridone9f.

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whereas the 1,3-oxazines11a-f should be the kineticallycontrolled ones; (ii) in the cyclization of ketenimines8a-dleading to the 4(3H)-pyridones9a-d, the first step (the [1,5]-X shift, X ) F, Cl, OH or SH) is rate-limiting; (iii) in thecyclization of ketenimines8e,f leading to the 4(3H)-pyridones9e,f (X ) NH2, PH2), the first step leading to the correspondingzwitterionic intermediates (INTe,f) is rate-limiting (note thatwhen X ) NH2, PH2, the 1,5-shift takes place in a two-stepprocess through the formation of such intermediates). Therefore,the exclusive formation of quinolin-4(3H)-ones5 in the experi-ments described above (modeled by the 4(3H)-pyridones9 inthe theoretical study) can be rationalized as resulting from theprevalence of the mechanistic pathway A of Scheme 3 underthermodynamic control.

A qualitative measuring of the reaction time required for thetotal transformation of the 1,3-oxazines11 into the pyridones9 can be inferred from the energy barriers gathered in Table 2.From the addition of∆E1 and (-∆Erxn11) the order of reactiontimes required for the different groups X is predicted to be,from lowest to highest, the following: Cl< F < SH < NH2 eOH < PH2.

In the ketenimines8a-f used in the computational study,the vinyl group joining the acyl and ketenimine functions models

the benzene ring of the ketenimines4. The lack of this benzenering does not account for the loss of aromaticity, which isexpected to take place in both the sigmatropic rearrangementof ketenimines4 leading to ketenes6 and the 6π-electrocy-clization to lead to the benzoxazines7. Therefore, it is expectedthat the corresponding energy barriers for the transfomation ofketenimines4 into the quinolin-4(3H)-ones5 and the benzox-azine7 will be higher than those obtained in the computationalstudy. However, we believe that this fact does not affectsignificantly the results of the computational study, as thepenalty for sacrificing the aromaticity would be similar for bothprocesses.22 But, more notably, the benzoxazines7 might bemore unstable, on thermodynamic grounds, than the correspond-ing oxazines11, and accordingly, the barrier for the conversionof benzoxazines7 into the corresponding quinolin-4(3H)-ones5 would essentially be the barrier between4 and 6, i.e., thatcorresponding to the [1,5]-X shift (note that, due to the retrievalof aromaticity, the barrier for the conversion of ketenes6 intothe quinolin-4(3H)-ones5 it is expected to be lower than thatof ketenes10 into the 4(3H)-pyridones9).

Characterization of the Pseudopericyclic Topology of theTransition States TS1, TS2, and TS3.An added value to thestudy of the mechanistic scheme for the two cyclization modesof the ketenimines8 is the characterization of the transition statesinvolved in these transformations as pseudopericyclic or not.Before elucidating the mechanistic pathways, we already pointedout that the structure of the ketenimines8 enables theseprocesses to show pseudopericyclic characteristics.23

The characterization of a process as pseudopericyclic has beenusually established on the basis of the planar or nearly planargeometry of the corresponding transition state.23b-f,24 In severalreports, the second-order perturbation interactions25 and the bondorder values of the NLMOs,25f,j from the NBO (natural bondorbital) analyses, have been used to show the disconnectionsin the orbital overlap of the transition states. The ACID method,by Herges et al.,26 has also proved to be a useful tool in thediscrimination between pericyclic and pseudopericyclic path-ways,25d,f,27and recently, the topological analysis of the electronlocalization function (ELF) has been proposed with this aim.28

(22) The penalty for sacrificing the aromaticity in related [1,5]-shifts inketenimines is around 10 kcal‚mol-1; see ref 12.

(23) Pseudopericyclic reactions lack cyclic orbital overlap and have fourcharacteristics, as stated by Birney: (1) all are allowed, (2) they havenonaromatic transition states, (3) they may have very low barriers, and (4)they may have planar transition states. (a) For Lemal’s definition of apseudopericyclic process, see: Ross, J. A.; Seiders, R. P.; Lemal, D. M.J.Am. Chem. Soc.1976, 98, 4325-4327. For other examples of pseudoperi-cyclic reactions, see, for example: (b) Birney, D. M.; Wagenseller, P. E.J.Am. Chem. Soc. 1994, 116, 6262-6270. (c) Birney, D. M.J. Org. Chem.1994, 59, 2557-2564. (d) Wagenseller, P. E.; Birney, D. M.; Roy,J. Org.Chem. 1995, 60, 2853-2859. (e) Birney, D. M.J. Org. Chem. 1996, 61,243-251. (f) Birney, D. M.; Xu, X.; Ham, S.Angew. Chem., Int. Ed.1999,38, 189-193. (g) Alajarı´n, M.; Sanchez-Andrada, P.; Cossı´o, F. P.; Arrieta,A.; Lecea, B.J. Org. Chem. 2001, 66, 8470-8477.

(24) See, for example: (a) Bornemann, H.; Wentrup, C.J. Org. Chem.2005, 70, 5862-5868. (b) Wei, H.-X.; Zhou, C.; Ham, H.; White, J. M.;Birney, D. M.Org. Lett.2004, 6, 4289-4292. (c) Birney, D. M.Org. Lett.2004, 6, 851-854. (d) Birney, D. M.J. Am. Chem. Soc. 2000, 122, 10917-10925. (e) Shumway, W.; Ham, S.; Moer, J.; Wittlesey, B. R.; Birney, D.M. J. Org. Chem. 2000, 65, 7731-7739. (f) Alajarın, M.; Vidal, A.;Sanchez-Andrada, P.; Tovar, F.; Ochoa, G.Org. Lett.2000, 2, 965-968.(g) Bibas, H. K.; Wentrup, C.J. Org. Chem.1998, 63, 2619-2626. (h)Birney, D. M.; Ham, S.; Unruh, G. R.J. Am. Chem. Soc.1997, 119, 4509-4517. (i) Luo, L.; Bartberger, M. D.; Dolbier, W. R., Jr.J. Am. Chem. Soc.1997, 119, 12366-12367. (j) Ham, S.; Birney, D. M.J. Org. Chem.1996,61, 3962-3968. (k) Koch, R.; Wong, M. H.; Wentrup, C.J. Org. Chem.1996, 61, 6809-6813. (l) Wagenseller, P. E.; Birney, D. M.; Roy, D.J.Org. Chem. 1995, 60, 2853-2859.

FIGURE 7. B3LYP/6-31+G*-optimized geometries of the transitionstructures found in the cyclization of the ketenimines8a-f to the 1,3-oxazines11a-f.

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One of the recognized characteristics of the pseudopericyclicreactions is that they occur through nonaromatic transition statesas the orbital disconnections prevent the aromaticity. Accord-ingly, the study of the magnetic properties of the transitionsstates and their relation with aromaticity is one of the most usefulcriteria to distinguish between pericyclic and pseudopericyclicmechanisms, particularly the analysis of its nuclear independentchemical shift (NICS) values pioneered by Schleyer et al.,29

who showed that large negative NICS values at the center ofthe ring under consideration are associated with aromaticcharacter, whereas positive NICS values are a convenientindicator of antiaromaticity. Cossı´o et al.,30 and afterward someof us,16,23g,25bhave found that the magnetic behavior of aromaticcompounds or transition states can be described by the variationof the NICS at different points above and below the molecular

plane, the intersection point being the (3,+1) ring critical pointas defined by Bader.31 Currently, the NICS values at differentpoints are frequently used to distinguish between pericyclic andpseudopericyclic transition states.13,25d,f,27b,c,32The ring currentmodel and the magnetic criteria, as showed by Cossı´o et al.,also allow the distinction among different kinds of aromatic-ity: σ-, π1-, andπ2-aromaticity.30e

On the basis of the geometries ofTS1a-d, TS2a-f, andTS3a-f and the results of the second-order perturbation

(25) (a) Sadavisam, D. V.; Birney, D. M.Org. Lett. 2005, 7, 5817-5820. (b) Alajarı´n, M.; Sanchez-Andrada, P.; Lo´pez-Leonardo, C.; AÄ lvarez,A. J. Org. Chem. 2005, 70, 7617-7623. (c) Fukushima, K.; Iwahashi, H.Heterocycles2005, 65, 2605-2618. (d) Cabaleiro-Lago, E. M.; Rodrı´guez-Otero, J.; Gonza´lez-Lopez, I.; Pen˜a-Gallego, A.; Hermida-Ramo´n, J. M.J.Phys. Chem. A2005, 109, 5636-5644. (e) Zhou, C.; Birney, D. M.J. Org.Chem. 2004, 69, 86-89. (f) Pena-Gallego, A.; Rodrı´guez-Otero, J.;Cabaleiro-Lago, E. M.J. Org. Chem.2004, 69, 7013-7017. (g) Rodriguez-Otero, J.; Cabaleiro-Lago, E. M.Chem.-Eur. J.2003, 9, 1837-1843. (h)De Lera, A. R.; Cossı´o, F. P.Angew. Chem., Int. Ed.2002, 41, 1150-1152. (i) Zhou, C.; Birney, D. M.J. Am. Chem. Soc.2002, 124, 5231-5241. (j) Fabian, W. M. F.; Kappe, C. O.; Bakulev, V. A.J. Org. Chem.2000, 65, 47-53. (k) Fabian, W. M. F.; Bakulev, V. A.; Kappe, C. O.J.Org. Chem.1998, 63, 5801-5805.

(26) (a) Herges, R.; Geuenich, D.J. Phys. Chem. A2001, 105, 3214-3220. (b) Herges, R.; Papafilippopoulos, A.Angew. Chem., Int. Ed.2001,40, 4671-4674. (c) Kimball, D. B.; Herges, R.; Haley, M. M.J. Am. Chem.Soc.2002, 124, 1572-1573.

TABLE 2. Energy Barriersa (∆E, kcal‚mol-1) Computed for the Alternative Cyclization Modes of Ketenimines 8a-f Leading to 9a-f and11a-fb

method ∆E1 ∆E2 ∆E3 ∆Erxn10 ∆Erxn9 ∆Erxn11

8af9a/11a(X ) F)HF/6-31G*c 37.30 15.14 18.84 7.40 -24.17 -1.48B3LYP/6-31+G* d 21.47 5.20 9.62 6.33 -20.09 -0.22

8bf9b/11b(X ) Cl)HF/6-31G*c 31.25 16.38 17.98 2.11 -28.23 -5.62B3LYP/6-31+G* d 15.76 3.50 9.06 5.54 -21.62 -2.49

8cf9c/11c(X ) OH)HF/6-31G*c 35.04 11.68 17.75 12.07 -27.44 -2.77B3LYP/6-31+G* d 22.90 2.76 8.50 10.23 -24.14 -2.65

8df9d/11d(X ) SH)HF/6-31G*c 35.17 13.52 16.43 0.70 -31.01 -8.63B3LYP/6-31+G* d 16.75 1.51 7.62 3.56 -25.36 -6.03

method ∆E1A ∆E1

B ∆E2 ∆E3 ∆Erxn1A ∆Erxn1

B ∆Erxn9 ∆Erxn11

8ef9e/11e(X ) NH2)HF/6-31G*c 29.63 0.64 6.02 14.59 14.75 -6.47 -30.41 -7.80B3LYP/6-31+G* d 18.09 3.45 6.35 5.77 - -27.58 -7.09

8ff9f/11f (X ) PH2)HF/6-31G*c 32.46 2.78 17.00 16.42 14.16 -18.59 -32.70 -14.11B3LYP/6-31+G* d 14.38 3.52 4.12 6.47 1.80 -4.23 -27.44 -11.85

a The energy barriers∆E1, ∆E3, and∆E1A have been calculated from the most stable conformer (around the C3-C4 and the C5-C6 single bonds) of

ketenimines8a-f, as usual.b See Figures 1 and 4 for the notation of the energy barriers.c Energies computed on the fully optimized HF/6-31G* geometries.The ZPVE corrections, computed at the same level, have been included. The ZPEs were not scaled.d Energies computed on the fully optimized B3LYP/6-31+G* geometries. The ZPVE corrections, computed at the same level, have been included. The ZPEs were not scaled.

SCHEME 5. Mechanistic Scheme Found at the HF/6-31G*Theoretical Level for the Cyclization of the Ketenimines 8e,fto the 4(3H)-Pyridones 9e,fa

a For 8f (X ) PH2), the same mechanistic pathway was found at theB3LYP/6-31+G* level.

SCHEME 6. Mechanistic Scheme Found at the B3LYP/6-31+G* Theoretical Level for the Cyclization of theKetenimine 8e to the 4(3H)-Pyridones 9e

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analyses, showing the delocalization energies of electrons fromfilled into empty NBOs, and the study of their magneticproperties, we have been able to establish the pseudopericyclicnature of these transition states. The optimized geometries ofTS1a-d, TS2a-f, andTS3a-f at the B3LYP/6-31+G* levelshowing the points used to evaluate the NICS values aredepicted in the Figures S1-S3 of the Supporting Information.

Transition Structures TS1a-d. The NBO analysis of thesetransition structures shows the new, partially formedσC1-X7bond resulting mainly from the interaction between a lone pairof the migrating heteroatom (which changes from a nonbondingsp2 orbital to a bonding sp3 orbital) and a p orbital of the C1dN3 system (the LUMO of the ketenimine moiety placed in themolecular plane) and not from the interaction between theσC6-X bond and theπC1dN3 system expected for a transitionstate of pericyclic nature (see selected interactions from thesecond-order perturbation analyses in the Supporting Informa-tion). The initial sp2 σC6-X bond orbital changes to anonbonding sp3 orbital for accommodating a lone pair in themigrating heteroatom of the final product. From these orbitaldisconnections the pseudopericyclic topology of these transitionstructures (TS1a-d) can thus be envisaged. These [1,5]-shiftscan be viewed as a swing of a negative group (the migratingheteroarom) between the two positive termini (C1 and C6).

We will now deal with the magnetic properties of thetransition statesTS1a-d. To our knowledge, there are noprecedents on the characterization as pseudopericyclic of [1,5]-shifts on the basis of the magnetic behavior of the correspondingtransition states. With the aim of comparing the magneticproperties ofTS1a-d with an adequate model of pericyclic[1,5]-shift, we have selected the transition stateTS1ref corre-sponding to the [1,5]-H shift in (Z)-1,3-pentadiene. Schleyerand Jiao, in their seminal publication in which they showedmagnetic evidence of the aromaticity of pericyclic transitionstructures,33 demonstrated that the NICS value (-16.6 ppm) atthe geometrical center of that transition state agrees with theirhigh aromaticity, previously established on the basis of geo-

metric, energetic, and others magnetic criteria.34 We have alsooptimizedTS1ref and calculated the NICS values along thez-axis perpendicular to the molecular plane which intersects the(3,+1) critical point. According to the behavior of the diamag-netic shielding along thisz-axis inTS1ref (see Figure 8A), wepropose to classify the aromaticity ofTS1ref asπ1-aromaticity,as there is only one maximum diamagnetic shielding above themolecular plane, which corresponds to the ring current circulat-ing on the side where the suprafacial transfer of hydrogen allowsa close proximity between the p atomic orbitals. The plot ofthe NICS values versusz for the transition structuresTS1a-ddiffers notably from that found forTS1ref, and the computedNICS values at the RCP (NICSRCP) and the maximum NICSvalues (NICSmax) of TS1a-d are much lower than thoseexpected for an aromatic transition state. These results can beseen in Table 3 and Figure 8A. Consequently, the transitionstructuresTS1a-d are clearly nonaromatic, confirming theirpseudopericyclic nature.

At this point, it is worth recalling the scarce precedents ofpseudopericyclic [1,5]-shifts that have been reported sofar.23e,24g,24k,25b,e,i,35Among these processes, there are only a fewexamples taking place in heterocumulenes: the degeneratedchlorine24k and hydrogen23e,35 rearrangement ofâ-(chlorocar-bonyl)vinyl ketene andâ-(formyl)vinyl ketene, respectively, andthe [1,5]-H shift in 1-propenyl ketene.24g The pseudopericycliccharacter of these transition states has been established on thebasis of their planar geometries.

Transition Structures TS2a-f. The formingσ-bond C2-C6 in TS2a-f is mainly due to the interaction between theπC1-C2 and theπ*C6-O12 (the LUMO of the ketenefragment placed in the molecular plane) natural localized orbitals(see Supporting Information), instead of the interaction betweenthe natural localized orbitalsπC1-C2/π*C5-C6 andπC5-C6/π*C1-C2 expected for a transition state of pericyclictopology. Besides, the p orbital at the ketene oxygen atomrehybridizes to an sp2 orbital to accommodate a lone pair inthe final product, whereas the newπCdO system results fromthe interaction between a lone pair at the oxygen atom and thep orbital at C6 perpendicular to the molecular plane. Therefore,there are disconnections in the CdO terminus. Obviously, inthe C5dC6 end no role interchange between nonbonding andbonding orbitals can take place, explaining the monorotatorynature of these transition structures as showed by their geom-etries. Again, the pseudopericyclic topology of these transitionstates (TS2a-f) was confirmed by their magnetic properties(see Table 3 and Figure 8B). We selected as the aromatic modelfor a pericyclic 6π-electrocyclization the transition state cor-responding to the cyclization ofcis-1,3,5-hexatriene to 1,3-cyclohexadiene,TS2ref. The shape of the plot curve (NICSversusz) for TS2ref, whose aromaticity was defined by Cossı´oet al. as the prototype ofπ1-aromaticity,30ediffers substantiallyof those obtained forTS2a-f (Figure 8B). Also, the lowNICSRCPand NICSmaxvalues clearly indicate the nonaromaticityof these transition states and point to its pseudopericyclic nature.

(27) (a) Kimball, D. M.; Weakley, T. J. R.; Herges, R.; Haley, M. M.J.Am. Chem. Soc.2002, 124, 13463-13473. (b) Cabaleiro-Lago E. M.;Rodrıguez-Otero, J.; Garcı´a-Lopez, R. M.; Pen˜a-Gallego, A.; Hermida-Ramon, J. M. Chem.- Eur. J.2005, 11, 5966-5974. (c) Cabaleiro-Lago,E. M.; Rodrıguez-Otero, J.; Varela-Varela, S. M.; Pen˜a-Gallego, A.;Hermida-Ramo´n, J. M. J. Org. Chem. 2005, 70, 3921-3928. (d) Pen˜a-Gallego, A.; Rodrı´guez-Otero, J.; Cabaleiro-Lago, E. M.Eur. J. Org. Chem.2005, 3228-3232.

(28) (a) Chamorro, E. E.; Notario, R.J. Phys. Chem. A2004, 108, 4099-4104. (b) Ca´rdenas, C.; Chamorro, E.; Notario, R.J. Phys. Chem. A2005,109, 4352-4358. (c) Matito, E.; Sola, M.; Duran, M.; Poater, J.J. Phys.Chem. B2005, 109, 7591-7593. (d) Rode, J. E.; Dobrowolski, J. Cz.J.Phys. Chem. A2006, 110, 207-218.

(29) (a) Schleyer, P. v. R.; Maerker, C.; Dransfeld, A.; Jiao, H.; Hommes,N. J. R. v. E.J. Am. Chem. Soc. 1996, 118, 6317-6318. (b) Schleyer, P.v. R.; Jiao, H.; Hommes, N. J. R. v. E.; Malkin, V. G.; Malkina, O. L.J.Am. Chem. Soc. 1997, 119, 12669-12670. (c) Schleyer, P. v. R.; Manoharn,M.; Wang, Z.-X.; Kiran, B.; Jiao, H.; Puchta, R.; Hommes, N. J. R. v. E.Org. Lett.2001, 3, 2465-2468. (d) See also Fallah-Bagher-Shaidaei, H.;Wannere, C. S.; Corminboeuf, C.; Puchta, R.; Schleyer, P. v. R.Org. Lett.2005, 7, 863-866 and references herein.

(30) (a) Morao, I.; Lecea, B.; Cossı´o, F. P.J. Org. Chem. 1997, 62,7033-7036. (b) Morao, I.; Cossı´o, F. P.J. Org. Chem. 1999, 64, 1868-1874. (c) Cossı´o, F. P.; Morao, I.; Jiao, H.; Scheleyer, P. v. R.J. Am. Chem.Soc. 1999, 121, 6737-6746. (d) Vivanco, S.; Lecea, B.; Arrieta, A.; Prieto,P.; Morao, I.; Linden, A.; Cossı´o, F. P.J. Am. Chem. Soc.2000, 122, 6078-6092. (e) de Lera, A. R.; Alvarez, R.; Lecea, B.; Torrado, A.; Cossı´o, F. P.Angew. Chem., Int. Ed. 2001, 40, 557-561.

(31) Bader, R. F. W.Atoms in MoleculessA Quantum Theory; ClarendonPress: Oxford, 1990; pp 13-52.

(32) See, for example: (a) Montero-Campillo, M. M.; Rodrı´guez-Otero,J.; Cabaleiro-Lago, E. M.J. Phys. Chem. A2004, 108, 8373-8377. (b)Zora, M. J. Org. Chem.2004, 69, 1940-1947. (c) Cossı´o, F. P.; Alonso,C.; Lecea, B.; Ayerbe, M.; Rubiales, G.; Palacios, F.J. Org. Chem.2006,71, 2839-2847.

(33) Jiao, H.; Schleyer, P. v. R.J. Chem. Soc., Faraday Trans. 1994,90, 1559-1567.

(34) Jiao, H.; Schleyer, P. v. R.J. Phys. Chem. 1998, 11, 655-662.(35) Reva, I.; Breda, S.; Roseiro, T.; Eusebio, E.; Fausto, R.J. Org.

Chem.2005, 70, 7701-7710.

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8136 J. Org. Chem., Vol. 71, No. 21, 2006

Closely related to these ring closures are the electrocycliza-tions of dienyl ketenes to 2,4-cyclohexadienones, which havebeen the subject of theoretical studies by Zora,32b,36 showingthat the corresponding transition structures adopt slightlynonplanar conformations, in contrast to the boatlike conforma-tion found forTS2ref. Those different geometries were ascribedto the fact that the LUMO orbital of the ketene moiety easily

interacts with the terminal CdC bond without disturbing somuch the planarity of the transition state. On the basis of thesegeometries and the NICS values computed at the center of theforming rings, Zora established the pseudopericyclic nature ofthe cyclization of dienyl ketenes, although, recently, thisassumption has provoked some controversy.27c Another relatedcyclization, that ofo-vinylphenylisocyanate to quinolin-2(1H)-one, occurring via a monorotatory transition state, has beenqualified by Dolbier as pseudopericyclic.24i

Transition Structures TS3a-f. The NBO analyses show thatin these transition structures the new partially formedσC1-O12 bond results mainly from the interaction between a lonepair of the carbonylic oxygen atom (which changes from anonbonding sp2 orbital to a bonding sp3 orbital) and a p orbitalof the C1dN3 system, and not from the interaction betweenthe πC6-O12 and theπC1dN3 systems expected for atransition state of pericyclic nature (see selected interactionsfrom the second-order perturbation analyses in the SupportingInformation). From the geometries of these transition structuresand the NBO analyses, it can be inferred that the lone pair atthe nitrogen atom N3 is changing from a nonbonding sp2 orbitalto a p orbital for forming part of the newπN3dC4 system,whereas the initial p orbital at the N3 atom changes to an sp2

orbital accommodating the lone pair in the final oxazine. In theC6-O12 terminus, the initial p orbital at the carbonylic oxygenatom rehibridizes to an sp3 orbital for accommodating a lonepair in the final oxazine. The nonaromaticity of these structureswas confirmed by the low absolute values of the NICS alongthe z axis, which are depicted in Figure 8C, along with thosecorresponding to the transition structureTS2ref for comparison.

There are several reports dealing with pseudopericyclicelectrocyclizations closely related to the cyclization of keten-imines8 to the 1,3-oxazines11,16,23g,24a,27bwhere the pseudo-pericyclic nature of these processes was established on the basisof the planar geometries of the corresponding transition statesor their magnetic properties.

(36) Zora, M.; Sahpaz, F.; Ozarslan, E.J. Mol. Structure (THEOCHEM)2002, 589-590, 111-112.

FIGURE 8. Plot of the calculated NICS values versusz for (A)transition structuresTS1a-d and TS1ref, (B) transition structuresTS2a-f andTS2ref, and (C) transition structuresTS3a-f and again,for comparative purposes,TS2ref. The NICS values have been obtainedat the GIAO-B3LYP/6-31+G*//B3LYP/6-31+G* level.

TABLE 3. NICS Values Computed at the Ring Critical Point ofthe Electron Density (NICSRCP) and Maximuma NICS Values alongthe z Axis (NICSMax) in ppm‚mol-1 in TS1a-d, TS2a-f, andTS3a-f Calculated at the GIAO-B3LYP/6-31+G*//B3LYP/6-31+G*Theoretical Level

transition structure NICSRCP NICSmax

TS1a(X ) F) -1.36 at 0.00 Å -1.36 at 0.00 ÅTS1b (X ) Cl) -3.24 at 0.00 Å -3.24 at 0.00 ÅTS1c(X ) OH) +0.28 at 0.05 Å +0.40 at-0.45 ÅTS1d (X ) SH) -0.13at-0.11 Å -0.84 at-0.86 ÅTS1refb -14.48 at-0.16 Å -16.27 at-0.41 ÅTS2a(X ) F) -3.01 at 0.07 Å -3.87 at-0.43 ÅTS2b (X ) Cl) -2.86 at 0.12 Å -4.82 at-0.63 ÅTS2c(X ) OH) -3.21 at 0.08 Å -3.57 at-0.41 ÅTS2d (X ) SH) -3.20 at 0.13 Å -4.71 at-0.62 ÅTS2ec (X ) NH2) -2.17 at 0.12 Å -3.25 at-0.63 ÅTS2f (X ) PH2) -2.83 at 0.14 Å -5.50 at-0.61 ÅTS2refd -14.92 at-0.09 Å -16.32 at-0.34 ÅTS3a(X ) F) +0.75 at 0.00 Å +0.87 at( 0.5 ÅTS3b (X ) Cl) +1.73 at 0.00 Å +1.84 at-0.24 ÅTS3c(X ) OH) +0.84 at-0.03 Å +1.29 at 0.47 ÅTS3d (X ) SH) +1.85 at-0.02 Å +2.34 at 0.23 ÅTS3e(X ) NH2) +0.82 at-0.04 Å +1.38 at 0.46 ÅTS3f (X ) PH2) +2.46 at 0.04 Å +3.11 at-0.21 Å

a Maximum NICS value by considering absolute values.b Transition statecorresponding to the [1,5]-H shift in 1,3-pentadiene.c NICS values computedat the B3LYP/6-31+G* level in TS2eoptimized at the HF/6-31G* level.d Transition state corresponding to the 6π-electrocyclic ring closure of 1,3,5-hexatriene leading to 1,3-cyclohexadiene.

Tandem Pseudopericyclic Reactions in Ketenimines

J. Org. Chem, Vol. 71, No. 21, 2006 8137

Conclusions

In this study a peculiar tandem sequence of two pseudoperi-cyclic events, [1,5]-X sigmatropic shift and further 6π-electro-cyclic ring closure, has been unraveled both on experimentaland theoretical bases. Different X groups have been analyzedwhen supported on aN-[2-(X-carbonyl)phenyl keteniminefragment. The relative migratory aptitude of such groups in thesigmatropic step has been determined experimentally as beingRSe ≈ RS . R2N ≈ ArO. The migrating aptitudes of thedifferent X groups at the acyl substituent in theN-(2-X-carbonyl)vinyl ketenimines considered in the theoretical studyis predicted to be PH2 > Cl > SH > NH2 > F > OH. The firststep of the transformation of theN-(2-X-carbonyl)vinyl keten-imines into the final 2-X-4(3H)-pyridones, the sigmatropic shift,is always rate-determining and may occur either in a concertedor stepwise manner (via zwitterionic intermediates), dependingon the nature of the migrating group X. A pseudopericyclictopology have been found for the transition states of some ofthe [1,5]-X migration (X ) F, Cl, OH, SH), and thosecorresponding to the second step, the 6π-electrocyclization ofthe ketene intermediates to the pyridones. An alternativecyclization mode of these ketenimines, the formation of 1,3-oxazines via an initial 6π-electrocyclic ring closure, has beenalso considered and calculated to be of pseudopericyclic nature.The marked modal selectivity of the whole system found inthe experiments (exclusive formation of quinolin-4(3H)-onesversus benzoxazines) could be rationalized on the basis of thecalculated energy barriers for the individual steps.

Experimental Section

Computational Methods.All calculations were carried out withthe Gaussian9837 and Gaussian0338 suite of programs. An intensivecharacterization of the potential energy surface was done at theHF/6-31G*39 theoretical level and then with the B3LYP40 functionalusing the 6-31+G* basis set. All the reported stationary points were

fully optimized by analytical gradient techniques. Harmonicfrequency calculations at each level of theory verified the identityof each stationary point as a minimum or a transition state andwere used to provide an estimation of the zero-point vibrationalenergies (ZPVE), which were not scaled. IRC calculations werecarried out in order to determine what minima each transitionstructure connects. Second-order perturbation analyses were achievedwith the NBO (natural bond orbital) method.41 NICS values wereobtained at the B3LYP/6-31+G* level with the GIAO (gauge-independent atomic orbital) method.42

Preparation of 2-Arylselenoquinolin-4(3H)-ones 5m-o. To asolution of the correspondingSe-aryl 2-azidoselenobenzoate2 (1mmol) in anhydrous toluene (15 mL) was added triphenylphosphine(0.26 g, 1 mmol), and the reaction mixture was stirred at roomtemperature for 4 h. Next, a solution of diphenylketene (0.19 g, 1mmol) or methylphenylketene (0.13 g, 1 mmol) in anhydroustoluene (2 mL) was added. The new reaction mixture was firststirred at room temperature for 15 min and then at refluxtemperature for 1 h. After cooling, the solvent was removed underreduced pressure. The resulting material was chromatographed onsilica gel using hexanes/diethyl ether (7:3, v/v) as eluent.

Some of the 2-arylselenoquinolin-4(3H)-ones5 prepared couldnot be obtained as crystalline solids. For these compounds, afterremoving the chromatographic solvents under reduced pressure, theresulting solids were triturated, dried at 50°C under high vacuumfor 24 h, and used as such for characterization.

3,3-Diphenyl-2-phenylselenoquinolin-4(3H)-one 5m:yield 62%;mp 182-184°C (yellow prisms, Et2O); IR (Nujol) 1683 (vs), 1599(w), 1580 (s), 1561 (vs), 1285 (m), 1154 (w), 1119 (w), 1068 (w),891 (w), 777 (w), 767 (m), 751 (m), 700 (s), 657 (m), 633 (s) cm-1;1H NMR (CDCl3, 300 MHz) δ 7.17-7.20 (m, 2 H), 7.35 (s, 10H), 7.40-7.43 (m, 3 H), 7.49 (td, 1 H,J ) 7.6, 1.4 Hz), 7.64-7.67 (m, 2 H), 7.77 (dd, 1 H,J ) 7.9, 1.5 Hz);13C NMR (CDCl3,75 MHz) δ 72.1 (s), 121.8 (s), 126.5, 127.4, 127.7, 128.6, 128.7,128.8, 129.0, 130.4, 135.8, 136.3, 137.5 (s), 146.2 (s), 178.9 (s),197.1 (s); MS (EI, 70 eV)m/z (rel int) 453 (M+ for 80Se, 12), 451(M+ for 78Se, 6), 296 (100). Anal. Calcd for C27H19NOSe(452.41): C, 71.68; H, 4.23; N, 3.10. Found: C, 71.57; H, 4.24;N, 3.01.

Preparation of 2-Aryloxyquinolin-4(3H)-ones 5p-s and 2-Ami-noquinolin-4(3H)-ones 5t-v. A solution of the corresponding2-(triphenylphosphoranylideneamino)benzoate3 (1 mmol) or the2-(triphenylphosphoranylideneamino)benzamide3 (1 mmol) inanhydrous dichloromethane (5 mL) was introduced in a glass tube,and a solution of diphenylketene (0.19 g, 1 mmol) or methylphe-nylketene (0.13 g, 1 mmol) in the same solvent (2 mL) was added.After stirring at room temperature for 15 min the solvent wasremoved to dryness under reduced pressure. The glass tube wassealed and the mixture containing the corresponding ketenimine4and triphenylphosphine oxide was heated at 230°C for 1 h. Aftercooling at room temperature, the crude mixture was dissolved indichloromethane (20 mL) and transferred to a round-bottom flask.Finally, the solvent was removed under reduced pressure and theresulting material was chromatographed on a silica gel column usinghexanes/diethyl ether as eluent.

Some of the 2-aryloxyquinolin-4(3H)-ones and 2-aminoquinolin-4(3H)-ones5 prepared could not be obtained as crystalline solids.

(37) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.;Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A.D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi,M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.;Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick,D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.;Ortiz, J. V.; Baboul, A. G.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz,P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe,M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Andres, J. L.;Gonzalez, C.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A.Gaussian98, Revision A.9; Gaussian, Inc.: Pittsburgh, PA, 1998.

(38) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,M. A.; Cheeseman, J. R.; Montgomery, J. A.; Vreven, T.; Kudin, K. N.;Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.;Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.;Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li,X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.;Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.;Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels,A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.;Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.;Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.: Piskorz,P.; Komaromi, L.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.;Peng, C. Y.; Nanayakkara, A.; Challacombe, M. P.; Gill, M. W.; Johnson,B. G.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A.Gaussian 03,Revision B.03; Gaussian, Inc.: Pittsburgh, PA, 2003.

(39) Hehre, W. J.; Radom, L.; Schleyer, P. v. R.; Pople, J. A. InAbInitio Molecular Orbital Theory; Wiley: New York, 1986, pp 71-82, andreferences therein.

(40) (a) Parr, R. G.; Yang, W.Density-Functional Theory of Atoms andMolecules; Oxford University Press: New York, 1989. (b) Bartolotti, L.J.; Fluchichk, K. InReViews in Computational Chemistry; Lipkowitz, K.B., Boyds, D. B., Eds.; VCH Publishers: New York, 1996; Vol. 7; pp 187-216. (c) Kohn, W.; Becke, A. D.; Parr, R. G.J. Phys. Chem. 1996, 100,12974-12980. (d) Ziegler, T.Chem. ReV. 1991, 91, 651-667.

(41) (a) Redd, A. E.; Weinstock, R. B.; Weinhold, F.J. Chem. Phys.1985, 83, 735-746. (b) Reed, A. E.; Curtiss, L. A.; Weinhold, F.Chem.ReV. 1988, 88, 899-926. (c) Reed, A. E.; Schleyer, P. v. R.J. Am. Chem.Soc. 1990, 112, 1434-1445.

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8138 J. Org. Chem., Vol. 71, No. 21, 2006

For these compounds, after removing the chromatographic solventsunder reduced pressure, the resulting solids were triturated, driedat 50 °C under high vacuum for 24 h, and used as such forcharacterization.

2-(4-Methylphenyloxy)-3,3-diphenylquinolin-4(3H)-one 5p:column chromatography, hexanes/diethyl ether (4:1, v/v); yield42%; mp 201-202°C (yellow prisms, Et2O); IR (Nujol) 1682 (vs),1641 (vs), 1598 (vs), 1504 (vs), 1268 (vs), 1244 (vs), 1197 (vs),1013 (m), 861 (w), 761 (s), 702 (s) cm-1; 1H NMR (CDCl3, 300MHz) δ 2.32 (s, 3 H), 6.93 (d, 2 H,J ) 8.3 Hz), 7.13 (d, 2 H,J) 8.3 Hz), 7.21 (t, 1 H,J ) 7.4 Hz), 7.26 (d, 1 H,J ) 8.1 Hz),7.30-7.36 (m, 10 H), 7.52 (td, 1 H,J ) 8.1, 1.5 Hz), 7.95 (d, 1 H,J ) 7.7 Hz); 13C NMR (CDCl3, 75 MHz) δ 20.9, 67.1 (s), 121.4,122.1 (s), 126.5, 127.3, 127.5, 128.0, 128.5, 129.6, 129.7, 135.0(s), 136.2, 138.9 (s), 146.6 (s), 150.2 (s), 168.5 (s), 196.7 (s); MS(EI, 70 eV)m/z (rel int) 403 (M+, 25), 77 (100). Anal. Calcd forC28H21NO2 (403.48): C, 83.35; H, 5.25; N, 3.47. Found: C, 83.18;H, 5.27; N, 3.32.

2-(N,N-Dimethyl)amino-3,3-diphenylquinolin-4(3H)-one 5t:column chromatography, hexanes/diethyl ether (2:3, v/v); yield36%; mp 242-244°C (yellow prisms, Et2O); IR (Nujol) 1670 (s),1599 (m), 1544 (vs), 1492 (m), 1393 (s), 1292 (m), 1269 (m), 1217(w), 1177 (m), 1142 (m), 999 (w), 871 (w), 763 (m), 742 (w), 696(m) cm-1; 1H NMR (CDCl3, 400 MHz)δ 2.80 (s, 6 H), 6.90 (t, 1H, J ) 7.4 Hz), 7.23-7.25 (m, 1 H), 7.27-7.35 (m, 6 H), 7.43-7.47 (m, 5 H), 7.67 (dd, 1 H,J ) 7.8, 1.3 Hz);13C NMR (CDCl3,100 MHz) δ 40.0, 66.1 (s), 118.6 (s), 122.6, 125.9, 127.2, 127.8,

128.7, 129.2, 136.3, 137.4 (s), 151.4 (s), 166.3 (s), 196.9 (s); MS(EI, 70 eV)m/z (rel int) 340 (M+, 100). Anal. Calcd for C23H20N2O(340.42): C, 81.15; H, 5.92; N, 8.23. Found: C, 81.01; H, 5.77;N, 8.34.

Acknowledgment. We are grateful to the “Ministerio deEducacio´n y Ciencia” of Spain and FEDER (Project CTQ2005-02323/BQU) and the “Fundacio´n Seneca-CARM” (Project PI-1/00749/FS/01) for funding. M.-M.O. thanks Fundacio´n Caja-murcia for a fellowship.

Supporting Information Available: Experimental details forthe synthesis of compounds2k-q, 3k-q, and 4a and theircharacterization (NMR, IR, MS, elemental analyses); spectroscopicdata for compounds5n-o, 5q-s, and5u,v; Table S1, includingthe chief electronic and energetic features for all stationary pointsdiscussed in the text; Cartesian coordinates of local minima andtransition structures discussed in the text; Table S2, includingselected interaction from the second-order perturbation theoryanalysis of TS1a-d, TS2a-f, and TS3a-f; Figures S1-S3,showing the B3LYP/6-31+G*-optimized geometries ofTS1a-d,TS1ref, TS2a-f, TS2ref, and TS3a-f and the points used toevaluate the NICS. This material is available free of charge via theInternet at http://pubs.acs.org.

JO061286E

Tandem Pseudopericyclic Reactions in Ketenimines

J. Org. Chem, Vol. 71, No. 21, 2006 8139